Immunogenic Complexes, Preparation Method Thereof And Use Of Same In Pharmaceutical Compositions

Abstract

The invention relates to a method of improving the immunogenicity of an immunogen, antigen or hapten, by means of coupling with a small support peptide. More specifically, the invention relates to a method of preparing an immunogenic complex, as well as the complexes that can be obtained using one such method, and to the use of said complexes as a medicament in order to increase the immunogenicity of an immunogen. The invention comprises, for example, a support peptide which is coupled with a peptide from protein G of the respiratory syncytial virus (RSV) and to the use thereof as a vaccine for the treatment of respiratory infections linked to RSV.

1 . A method for preparing an immunogenic complex in which an immunogen, antigen or hapten is associated with a support peptide to form the aforesaid immunogenic complex, wherein the aforesaid support peptide consists of a peptide of less than 10 amino acids comprising at least the peptide of sequence SEQ ID NO 2. 
     
     
         2 . A method according to  claim 1 , wherein the aforesaid support peptide of less than 10 amino acids consists of the peptide coded by SEQ ID NO 2. 
     
     
         3 . A method according to  claim 1  or  2 , wherein the aforesaid association consists of covalent coupling between the aforesaid peptide support and the aforesaid immunogen. 
     
     
         4 . A method according to  claim 3 , wherein the aforesaid support peptide is coupled at the N-terminal end of the aforesaid immunogen when the aforesaid immunogen is a peptide. 
     
     
         5 . A method according to  claim 4 , wherein the aforesaid covalent coupling is carried out by recombinant DNA technology. 
     
     
         6 . A method according to  claim 3  or  4 , wherein the aforesaid covalent coupling is carried out by the chemical route. 
     
     
         7 . A method according to one of the  claims 1  to  6 , wherein the immunogen is an antigen arising from bacteria, parasites and/or viruses. 
     
     
         8 . A method according to  claim 7 , wherein the immunogen is a respiratory syncytial virus (RSV) surface protein or glycoprotein, a protein of a sequence having at least 80% identity with the sequence of the aforesaid RSV surface protein or a fragment of at least 10 consecutive amino acids of the aforesaid RSV surface protein, the aforesaid protein of a sequence having at least 80% identity or the aforesaid fragment being capable of inducing the production of specific antibodies directed against said protein or said fragment after the administration thereof in a mammal. 
     
     
         9 . A method according to  claim 8 , wherein the immunogen is the human RSV type A or B G protein or the bovine RSV G protein, a protein of a sequence having at least 80% identity with the sequence of the aforesaid G protein or a fragment of the aforesaid G protein of at least 10 amino acids. 
     
     
         10 . A method according to  claim 9 , wherein the immunogen is the polypeptide of the sequence between residues 130 and 230 of the RSV G protein, ends included, or of a sequence having at least 80% identity with the aforesaid sequence between residues 130 and 230, or a fragment of the aforesaid G protein of at least 10 amino acids. 
     
     
         11 . A method according to  claim 10 , wherein the immunogen is the polypeptide of sequence SEQ ID NO 3. 
     
     
         12 . An immunogenic complex obtained by the implementation of the method according to one of the  claims 8  to  11 . 
     
     
         13 . An immunogenic complex comprising an immunogen, antigen or hapten, associated with a support peptide, wherein:
 the aforesaid immunogen is associated, preferably coupled by a covalent link, with a support peptide of less than 10 amino acids comprising at least the peptide of sequence SEQ ID NO 2; and wherein   the immunogen is a syncytial respiratory virus (RSV) surface protein or glycoprotein, more particularly F or G, or is of a sequence having at least 80% identity with the sequence of the aforesaid RSV surface protein, capable of inducing the production of specific antibodies directed against said protein of a sequence having at least 80% identity after the administration thereof in a mammal.   
     
     
         14 . A complex according to  claim 13 , wherein the aforesaid support peptide is the peptide of sequence SEQ ID NO 2. 
     
     
         15 . A complex according to  claim 12  or  13 , wherein it is a MEFG2Na complex of sequence SEQ ID NO 4, or an immunogenic complex whose sequence presents in position 1 to 3 the sequence SEQ ID NO 2 followed by:
 a sequence having at least 80% identity with sequence SEQ ID NO 3, preferably 85%, 90%, 95% or 98% identity with sequence SEQ ID NO 3.   
     
     
         16 . A complex according to  claim 15 , of sequence SEQ ID NO 4. 
     
     
         17 . A nucleic acid coding for an immunogenic complex according to one of the  claims 13  to  16 . 
     
     
         18 . A nucleic acid according to  claim 17  coding for the immunogenic complex of sequence SEQ ID NO 4. 
     
     
         19 . A complex according to one of the  claims 12  to  16 , or a nucleic acid according to  claim 17  or  18 , used as a drug. 
     
     
         20 . The use of an immunogenic complex according to one of the  claims 12  to  16 , or a nucleic acid according to  claim 17  or  18 , for the preparation of a pharmaceutical composition intended for the treatment or prevention of RSV-related respiratory infections.